(a) Field of the Invention
This invention relates to an improved production process of N-monosubstituted amide compounds. It also relates to a novel production process of N,N-disubstituted amide compounds.
(b) Description of the Prior Art
Since N-substituted amide compounds generally contain well-balanced hydrophilic groups and hydrophobic groups in their molecules, they have such advantages that their miscibility with various substances are good, they exhibit strong resistance to hydrolysis, and unsaturated amide compounds pertain excellent homopolymerization or copolymerization property. Owing to such advantages, a wide variety of application fields are known for N-substituted amine compounds, including adhesive, paint, paper-processing agents, textile-processing agents, emulsion, urethane stiffeners, pigment dispersants, plastics additives, polymeric coagulants, ion-exchange resins, etc. They are also useful as starting materials or intermediates for or even final products of compounds having a complex structure such as pharmaceutical products, agricultural chemicals, amino acids, naturally-occurring substances, etc. and, also, as a starting material for the production of amines. Notwithstanding such advantages and usefulness of N-substituted amide compounds, they have not yet been used in a great quantity as no inexpensive industrial production process has yet been established for N-substituted amide compounds.
As known industrial production processes of N-substituted amide compounds, may be mentioned a production process relying upon the reaction between a carboxylic chloride and an amine as well as another production process which makes use of the Ritter reaction. However, under the current circumstances, N-substituted amide compounds produced in accordance with such conventional processes are either expensive or are limited to certain specific types, thereby limiting their applications to specific fields.
Furthermore, as a general production process of N-substituted amide compounds, there has been known to convert an amide compound to an amide compound substituted by one or more alkali metals under the influence of a strongly basic substance such as alkali metal alkoxide and then to convert the thus-alkali metal substituted amide compound to an N-substituted amide compound under the influence of a halogen-substituted compound such as alkyl halide. Reference may, for example, be made to Hikkinbottom, W. J., Reactions of Organic Compounds (Vol. 3), Longmans, Green and Co., (1957) and U.S. Pat. No. 3,084,191. However, this process involves varied inconvenience such that the process comprises two steps; it requires as a reaction solvent a protonic solvent having high reactivity in the presence of a basic catalyst with a halogen-substituted compound, such as liquid ammonia or an alcohol; it also requires an extremely strong basic substance which is irksome to handle, such as an alkali metal amide, alkali metal hydride, or alkali metal alkoxide. Due to such inconvenience, as shown in Comparative Examples 1 through 3 which will be described later, this process involves such problems that the yield of an intended final product is low, the halogen-substituted compounds reactable with the alkali metal substituted amide compound are limited to specific ones and the reaction product is exclusively an N-monosubstituted amide compound and, where an N,N-disubstituted amide compound is intended, the process has to be repeated similarly. For the reasons mentioned above, this process has not been adopted in an industrial large scale as a production process for general N-substituted amide compounds.
Alternatively, as disclosed on Page 266 of G. L. Isele, A. Luttringhous, Synthesis 1971 (5), it has been known to use a two-step production process in which, after reacting an amide compound with a strongly basic substance in an aprotic polar solvent to form an alkali metal-substituted amide compound, the alkali metal-substituted amide compound is reacted with a halogen-substituted compound such as an alkyl halide to obtain an N-alkyl-substituted-amide compound. However, even if this process was followed, no satisfactory results have been obtained as described in Comparative Example 2.
In addition, USSR Certificate of Inventorship No. 667,547 discloses a production process of N-alkylated organic compounds, in which a basic substance such as caustic soda is added in the form of an aqueous solution and the substitution reaction is initiated while keeping all the basic substance in a liquid state. According to the disclosure of the certificate, it is mentioned that, in the above process, the presence of water in the reaction mixture is extremely convenient for the proceeding of the reaction. According to a study made by the present inventors, as will be apparent from a comparison between Examples 1, 3 and 4 and Comparative Example 4 which will also be described later, this process is accompanied by a considerable occurrence of reaction by-products, whereby making its selectivity of an intended N-substituted amide compound poor and, depending on an N-substituted amide compound intended, resulting in a considerable reduction of its yield.
In the case where the starting amide compound, to which the present invention is directed, is an unsaturated compound, N,N-substitution reaction does not take place in the same manner as in the case of the saturated compounds disclosed in Johnstone et al., Tetrahedron, Vol. 35, pages 2169-2173. In this regard, the general alkylation procedure recited on page 2173, left column, of the Johnstone et al. reference, shows an example of the use of potassium hydroxide in an amount of 4 m moles per replaceable hydrogen of substrate, i.e., 8 moles per one mole of the substrate. However, in the case where such a large amount of potassium is used in an N-substitution reaction of unsaturated compounds, polymerization and other side reactions take place.